Long Interspersed Nuclear Elements (LINES or L1 s) are a family of retrotransposons that comprise nearly 17% of the human genome. Although the majority of L1 s cannot retrotranspose, an estimated 60 elements remain retrotransposition competent. L1 retrotransposition can be mutagenic, and deleterious insertions have resulted in a variety of diseases including cancer. L1s encode two proteins, ORF-1 and ORF-2. ORF-2 is relatively well characterized; it has endonuclease activity presumably to make nicks in chromasomal DNA to initiate integration. It also contains reverse transcriptase activity in order to synthesize the copy DNA. Both of these functions are crucial for L1 retrotransposition. In contrast, although a number of studies aimed at characterizing ORF-1 have been reported, the exact role of ORF-1 in L1 retrotransposition remains to be elucidated. Utilizing a number of molecular biological and biochemical approaches we will study the various properties of ORF-1 protein. These studies will help to define its' role in L1 retrotransposition.